The synthesis and secretion of the serum retinol binding protein (RBP) is subject to regulation. In the liver, the major site of RBP synthesis, vitA influences transcription of the RBP gene and i required for its secretion. It is found in the liver in association with transthyretin (TTR) two which it also binds in the serum. TTR-deficient mutant mice show elevated translation rates of hepatic RBP and accumulate the protein, possibly in the ER. This project is designed to study RBP synthesis and secretion in TTR-mutant mice, as well as in mice deficient in the cellular retinal binding protein, CRBP-1. These biochemical studies will focus will focus on the liver and on Sertoli cells, which synthesize and secrete RBP but not TTR. To facilitate the analysis of RBP metabolism, the mutant mice will be crossed with the SV40 temperature-sensitive T antigen transgenic mouse, the "immortomouse", and permanent hepatocyte and Sertoli cell lines will be established. The TTR-deficient mice have the unusual phenotype of enhanced resistance to hypervitaminosis A. The likely possibility that this is related to changes in hepatic RBP and retinol metabolism will be explored.